In 1963 we reported the isolation of a diabetogenic peptide from urine of patients with lipoatrophic diabetes. Subsequently we have found a similar peptide in the urine of 90 percent of proteinuric diabetic patients. This peptide is absent from the urine of proteinuric nondiabetic, nonproteinuric diabetics and healthy subjects. We have reported the isolation of a similar peptide from adenohypophysis of beef, sheep and hogs. The compound from all of the above sources is diabetogenic and antagonizes the action of exogenous insulin in men and dogs. It also inhibits the effect of insulin in vitro. Current studies have disclosed that the peptide induces both hyperinsulinemia and hyperglycemia in dogs. Recently, we have reported the isolation of a diabetogenic peptide from human pituitaries. It has been partially purified and found to be similar to the peptide excreted by proteinuric diabetic patients. Its diabetogenic potency is much greater than human growth hormone or ovine prolactin. The molecular weight of the peptide is 20,600 and its isoelectric point is pH 4.1. Our objectives are (1) to further purify the peptide as a single chemical entity (2) to determine its physicochemical and biological properties (3) to develop a radioimmunoassay for the peptide (4) to determine the blood levels of the peptide of diabetics, prediabetics and healthy people (5) to study its mechanism of secretion and possible role in the pathogenesis of diabetes mellitus in man.